This program involves the investigation of the biological effects of accelerated heavy particles (such as carbon, neon, and argon ions) and the optimization of methods whereby these beams can be applied to the treatment of human cancer. The principal accelerator used in Bevalac, a unique machine capable of producing biomedical heavy-ion beams to 1 GeV/nucleon kinetic energy. The rationale for using heavy ions in therapy is based on (a) the physical characteristics of charged particle beams which can be used to deliver a greater biologically effective dose to deep-seated tumors than is currently available with conventional radiation modalities, and (b) the fact that heavy ions reduce sensitivity differences between anoxic tumor cells and normal tissues. Molecular and cellular studies include the effects on survival of mammalian cells in tissue culture and the modification of these effects by oxygen. The nature of sublethal and potentially lethal lesions will also be studied. Tissue radiobiology encompasses studies of the effects of heavy-ion beams on normal mammalian tissues. The radiobiological response of such tissues (i.e., skin, lung, spinal cord, gut, kidney) are needed to provide the therapist with a basis for estimating safe dose levels to radiation fields which encompass critical normal organs. Special attention is given to chronic effects from fractionated exposures because they relate to application of beams to human therapy. Studies of tumor growth and kinetics investigate heavy-ion induced changes in cell proliferation in vivo and in vitro. Heavy-ion physics is essential for human applications, because dose must be measured precisely and accurately, and the therapeutic administration of heavy particles depends on a computerized beam delivery system.